Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma.

BACKGROUND: Lung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants. METHODS: We utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n = 660). The top significant metabolite principal component (PCLF) was evaluated in an independent cross-sectional child cohort, the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n = 1151) and evaluated for association with spirometric measures. Using meta-analysis of CAMP and GACRS, we identified associations between PCLF and microRNA, and SNPs in their target genes. Statistical significance was determined using an false discovery rate-adjusted Q-value. FINDINGS: The top metabolite principal component, PCLF, was significantly associated with better LFTs after multiple-testing correction (Q-value = 0.03). PCLF is composed of the urea cycle, caffeine, corticosteroid, carnitine, and potential microbial (secondary bile acid, tryptophan, linoleate, histidine metabolism) metabolites. Higher levels of PCLF were also associated with increases in lung function measures and decreased circulating neutrophil percentage in both CAMP and GACRS. PCLF was also significantly associated with microRNA miR-143-3p, and SNPs in three miR-143-3p target genes; CCZ1 (P-value = 2.6 × 10-5), SLC8A1 (P-value = 3.9 × 10-5); and TENM4 (P-value = 4.9 × 10-5). INTERPRETATION: This study reveals associations between metabolites, miR-143-3p and LFTs in children with asthma, offering insights into asthma physiology and possible interventions to enhance lung function and long-term health. FUNDING: Molecular data for CAMP and GACRS via the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung, and Blood Institute (NHLBI).

Contraceptive Use Among Traditional Medicare And Medicare Advantage Enrollees.

Medicare is the primary source of health insurance coverage for reproductive-age people with Social Security Disability Insurance. However, Medicare does not require contraceptive coverage for pregnancy prevention, and little is known about contraceptive use in traditional Medicare and Medicare Advantage. We analyzed Medicare and Optum data to assess variations in contraceptive use and methods used by traditional Medicare and Medicare Advantage enrollees, as well as among enrollees with and without noncontraceptive clinical indications. Clinically indicated contraceptives are used for reasons other than pregnancy prevention, including menstrual regulation or to treat acne, menorrhagia, and endometriosis. Contraceptive use was higher among Medicare Advantage enrollees than traditional Medicare enrollees, but use in both populations was low compared with contraceptive use among Medicaid enrollees. We found significant variation by Medicare type with respect to contraceptive methods used. Relative to traditional Medicare, the probability of long-acting reversible contraception was more than three times higher in Medicare Advantage, and the probability of tubal sterilization was more than ten times higher. Overall, Medicare enrollees with noncontraceptive clinical indications had twice the probability of contraceptive use as those without them. Medicare coverage of all contraceptive methods without cost sharing would help address financial barriers to contraceptives and support the reproductive autonomy of disabled enrollees.

A new small molecule DoNA binding to CAG repeat RNA.

We here report a new molecule DoNA binding to a CAG repeat RNA. DoNA is a dimer of the NA molecule that we previously reported. NA binds with high affinity to a CAG repeat DNA but not significantly to a CAG repeat RNA. Binding analyses using SPR and CSI-TOF MS indicated a significant increase in the affinity of DoNA to a single stranded CAG repeat RNA compared to NA. Systematic investigation of the RNA motifs bound by DoNA using hairpin RNA models revealed that DoNA binds to the CAG units at overhang and terminal positions, and notably, it binds to the structurally flexible internal and hairpin loop region.

Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

BACKGROUND: The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). METHODS: A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. RESULTS: In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. CONCLUSIONS: The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

Myosin heavy chain isoform expression and meat quality characteristics of different muscles in yak (Bos grunniens).

Myosin heavy chain (MHC) isoforms and meat quality characteristics of different muscles were investigated to explore their potential relationships in yaks. Results showed that semitendinosus (ST), longissimus thoracis (LT), and infraspinatus (IS) have a greater ratio of MHC IIb (47.84%), MHC IIa (73.27%), and MHC I (24.26%), respectively, than the other two muscles. Compared with LT or ST, IS exhibited more intense color, greater water-holding capacity, and initial tenderness with higher intermuscular fat (IMF) and collagen (of lower cross-linking level), presenting overall better quality. Variations in MHC isoforms accounted for the muscle-specific meat quality. Specifically, MHC I was positively associated with redness, myoglobin, IMF, collagen, pH, and thermal stability and negatively associated with myofibril fragmentation index, fiber thickness, collagen cross-linking, and drip loss. These results provide insights into the relationships between MHC isoforms and meat quality in yaks and the MHC I isoform has an extensive influence on meat quality.

OMICmAge: An integrative multi-omics approach to quantify biological age with electronic medical records.

Biological aging is a multifactorial process involving complex interactions of cellular and biochemical processes that is reflected in omic profiles. Using common clinical laboratory measures in ~30,000 individuals from the MGB-Biobank, we developed a robust, predictive biological aging phenotype, EMRAge, that balances clinical biomarkers with overall mortality risk and can be broadly recapitulated across EMRs. We then applied elastic-net regression to model EMRAge with DNA-methylation (DNAm) and multiple omics, generating DNAmEMRAge and OMICmAge, respectively. Both biomarkers demonstrated strong associations with chronic diseases and mortality that outperform current biomarkers across our discovery (MGB-ABC, n=3,451) and validation (TruDiagnostic, n=12,666) cohorts. Through the use of epigenetic biomarker proxies, OMICmAge has the unique advantage of expanding the predictive search space to include epigenomic, proteomic, metabolomic, and clinical data while distilling this in a measure with DNAm alone, providing opportunities to identify clinically-relevant interconnections central to the aging process.

The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseases.

BACKGROUND: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the existing physiologic state, unobserved via current clinical measures. Furthermore, metabolomics profiling during acute disease can be influenced by confounding factors such as indications, medical treatments, and lifestyles. METHODS: We employed metabolomic profiling to cluster infection-free individuals and assessed their relationship with COVID severity and influenza incidence/recurrence. FINDINGS: We identified a metabolomic susceptibility endotype that was strongly associated with both severe COVID (ORICUadmission = 6.7, p-value = 1.2 × 10-08, ORmortality = 4.7, p-value = 1.6 × 10-04) and influenza (ORincidence = 2.9; p-values = 2.2 × 10-4, ßrecurrence = 1.03; p-value = 5.1 × 10-3). We observed similar severity associations when recapitulating this susceptibility endotype using metabolomics from individuals during and after acute COVID infection. We demonstrate the value of using metabolomic endotyping to identify a metabolically susceptible group for two-and potentially more-IDs that are driven by increases in specific amino acids, including microbial-related metabolites such as tryptophan, bile acids, histidine, polyamine, phenylalanine, and tyrosine metabolism, as well as carbohydrates involved in glycolysis. INTERPRETATIONS: These metabolites may be identified prior to infection to enable protective measures for these individuals. FUNDING: The Longitudinal EMR and Omics COVID-19 Cohort (LEOCC) and metabolomic profiling were supported by the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health.

A meta-analysis of immune-cell fractions at high resolution reveals novel associations with common phenotypes and health outcomes.

BACKGROUND: Changes in cell-type composition of tissues are associated with a wide range of diseases and environmental risk factors and may be causally implicated in disease development and progression. However, these shifts in cell-type fractions are often of a low magnitude, or involve similar cell subtypes, making their reliable identification challenging. DNA methylation profiling in a tissue like blood is a promising approach to discover shifts in cell-type abundance, yet studies have only been performed at a relatively low cellular resolution and in isolation, limiting their power to detect shifts in tissue composition. METHODS: Here we derive a DNA methylation reference matrix for 12 immune-cell types in human blood and extensively validate it with flow-cytometric count data and in whole-genome bisulfite sequencing data of sorted cells. Using this reference matrix, we perform a directional Stouffer and fixed effects meta-analysis comprising 23,053 blood samples from 22 different cohorts, to comprehensively map associations between the 12 immune-cell fractions and common phenotypes. In a separate cohort of 4386 blood samples, we assess associations between immune-cell fractions and health outcomes. RESULTS: Our meta-analysis reveals many associations of cell-type fractions with age, sex, smoking and obesity, many of which we validate with single-cell RNA sequencing. We discover that naïve and regulatory T-cell subsets are higher in women compared to men, while the reverse is true for monocyte, natural killer, basophil, and eosinophil fractions. Decreased natural killer counts associated with smoking, obesity, and stress levels, while an increased count correlates with exercise and sleep. Analysis of health outcomes revealed that increased naïve CD4 + T-cell and N-cell fractions associated with a reduced risk of all-cause mortality independently of all major epidemiological risk factors and baseline co-morbidity. A machine learning predictor built only with immune-cell fractions achieved a C-index value for all-cause mortality of 0.69 (95%CI 0.67-0.72), which increased to 0.83 (0.80-0.86) upon inclusion of epidemiological risk factors and baseline co-morbidity. CONCLUSIONS: This work contributes an extensively validated high-resolution DNAm reference matrix for blood, which is made freely available, and uses it to generate a comprehensive map of associations between immune-cell fractions and common phenotypes, including health outcomes.

Sex-related differences in the prevalence of substance use disorders, treatment, and overdose among parents with young children.

Introduction: Risk factors and treatment rates for substance use disorders (SUDs) differ by sex. Females often have greater childcare and household responsibilities than males, which may inhibit SUD treatment. We examined how SUD, medication for opioid use disorder (MOUD) receipt, and overdose rates differ by sex among parents with young children (<5 years). Methods: Using deidentified national administrative healthcare data from Optum's Clinformatics® Data Mart Database version 8.1 (2007-2021), we identified parents aged 26-64 continuously enrolled in commercial insurance for ≥ 30 days and linked to ≥ 1 dependent child < 5 years from January 1, 2016-February 29, 2020. We used generalized estimating equations to estimate the average predicted prevalence of SUD diagnosis, MOUD receipt after opioid use disorder (OUD) diagnosis, and overdose by parent sex in any month, adjusting for age, race/ethnicity, state of residence, enrollment month, and mental health conditions. Results: From 2016 to 2020, there were 2,241,795 parents with a dependent child < 5 years, including 1,155,252 (51.5%) females and 1,086,543 (48.5%) males. Male parents had a higher average predicted prevalence of an SUD diagnosis (11.1% [11, 11.16]) than female parents (5.5% [5.48, 5.58]). Among parents with OUD, the average predicted prevalence of receiving MOUD was 27.4% [26.1, 28.63] among male and 19.7% [18.34, 21.04] among female parents, with no difference in overdose rates by sex. Conclusion: Female parents are less likely to be diagnosed with an SUD or receive MOUD than male parents. Removing policies that criminalize parental SUD and addressing childcare-related barriers may improve SUD identification and treatment.

Phage N15-Based Vectors for Gene Cloning and Expression in Bacteria and Mammalian Cells.

Bacteriophage N15 is the first virus known to deliver linear prophage into Escherichia coli. During its lysogenic cycle, N15 protelomerase (TelN) resolves its telomerase occupancy site (tos) into hairpin telomeres. This protects the N15 prophage from bacterial exonuclease degradation, enabling it to stably replicate as a linear plasmid in E. coli. Interestingly, purely proteinaceous TelN can retain phage DNA linearization and hairpin formation without involving host- or phage-derived intermediates or cofactors in the heterologous environment. This unique feature has led to the advent of synthetic linear DNA vector systems derived from the TelN-tos module for the genetic engineering of bacterial and mammalian cells. This review will focus on the development and advantages of N15-based novel cloning and expression vectors in the bacterial and mammalian environments. To date, N15 is the most widely exploited molecular tool for the development of linear vector systems, especially the production of therapeutically useful miniDNA vectors without a bacterial backbone. Compared to typical circular plasmids, linear N15-based plasmids display remarkable cloning fidelity in propagating unstable repetitive DNA sequences and large genomic fragments. Additionally, TelN-linearized vectors with the relevant origin of replication can replicate extrachromosomally and retain transgenes functionality in bacterial and mammalian cells without compromising host cell viability. Currently, this DNA linearization system has shown robust results in the development of gene delivery vehicles, DNA vaccines and engineering mammalian cells against infectious diseases or cancers, highlighting its multifaceted importance in genetic studies and gene medicine.

Effect of slaughter age and postmortem aging time on tenderness and water-holding capacity of yak (Bos grunniens) longissimus thoracis muscle.

The present study investigated the effect of slaughter age (2.43 ± 0.20, 4.15 ± 0.19, 6.62 ± 0.18, 10.59 ± 0.74 years) and postmortem aging time (1, 24, and 72 h) on the tenderness and water-holding capacity (WHC) of yak longissimus thoracis muscles to determine the most suitable age for slaughter to ensure product consistency. Under conventional postmortem aging conditions (4 °C), muscles of each age group exhibited the effect of cold shortening. Once the cold shortening occurred, the age effect on thickening muscle fiber and developing cross-links of collagen, considered to intensify the meat toughness, became less important. Owing to greater carcass weight and intramuscular fat, muscles of the older carcass (over 6-year-old) were less influenced by the cold shortening effect during the chilling process and showed lessened sarcomere contraction, delayed formation of drip loss channels, and increased level of myofibril fragmentation index (MFI) and myofiber structural disintegration, resulting in greater tenderness and WHC, especially 6-7 years group. Aging of 72 h structurally disintegrated the collagen cross-linking and integrity of muscle fibers and elevated the MFI, improving the meat tenderness. Therefore, the suitable slaughter age for yak is 6-7 years old and after 72 h aging, improved quality of yak meat can be obtained.

Duration of medication for opioid use disorder during pregnancy and postpartum by race/ethnicity: Results from 6 state Medicaid programs.

BACKGROUND: Medication for opioid use disorder (MOUD) is evidence-based treatment during pregnancy and postpartum. Prior studies show racial/ethnic differences in receipt of MOUD during pregnancy. Fewer studies have examined racial/ethnic differences in MOUD receipt and duration during the first year postpartum and in the type of MOUD received during pregnancy and postpartum. METHODS: We used Medicaid administrative data from 6 states to compare the percentage of women with any MOUD and the average proportion of days covered (PDC) with MOUD, overall and by type of MOUD, during pregnancy and four postpartum periods (1-90 days, 91-180 days, 181-270 days, and 271-360 days postpartum) among White non-Hispanic, Black non-Hispanic, and Hispanic women diagnosed with OUD. RESULTS: White non-Hispanic women were more likely to receive any MOUD during pregnancy and all postpartum periods compared to Hispanic and Black non-Hispanic women. For all MOUD types combined and for buprenorphine, White non-Hispanic women had the highest average PDC during pregnancy and each postpartum period, followed by Hispanic women and Black non-Hispanic women (e.g., for all MOUD types, 0.49 vs. 0.41 vs. 0.23 PDC, respectively, during days 1-90 postpartum). For methadone, White non-Hispanic and Hispanic women had similar average PDC during pregnancy and postpartum, and Black non-Hispanic women had substantially lower PDC. CONCLUSIONS: There are stark racial/ethnic differences in MOUD during pregnancy and the first year postpartum. Reducing these inequities is critical to improving health outcomes among pregnant and postpartum women with OUD.

Heteromerization of short-chain trans-prenyltransferase controls precursor allocation within a plastidial terpenoid network.

Terpenes are the largest and most diverse class of plant specialized metabolites. Sesterterpenes (C25), which are derived from the plastid methylerythritol phosphate pathway, were recently characterized in plants. In Arabidopsis thaliana, four genes encoding geranylfarnesyl diphosphate synthase (GFPPS) (AtGFPPS1 to 4) are responsible for the production of GFPP, which is the common precursor for sesterterpene biosynthesis. However, the interplay between sesterterpenes and other known terpenes remain elusive. Here, we first provide genetic evidence to demonstrate that GFPPSs are responsible for sesterterpene production in Arabidopsis. Blockage of the sesterterpene pathway at the GFPPS step increased the production of geranylgeranyl diphosphate (GGPP)-derived terpenes. Interestingly, co-expression of sesterTPSs in GFPPS-OE (overexpression) plants rescued the phenotypic changes of GFPPS-OE plants by restoring the endogenous GGPP. We further demonstrated that, in addition to precursor (DMAPP/IPP) competition by GFPPS and GGPP synthase (GGPPS) in plastids, GFPPS directly decreased the activity of GGPPS through protein-protein interaction, ultimately leading to GGPP deficiency in planta. Our study provides a new regulatory mechanism of the plastidial terpenoid network in plant cells.

Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.

Understanding the molecular underpinnings of disease severity and progression in human studies is necessary to develop metabolism-related preventative strategies for severe COVID-19. Metabolites and metabolic pathways that predispose individuals to severe disease are not well understood. In this study, we generated comprehensive plasma metabolomic profiles in >550 patients from the Longitudinal EMR and Omics COVID-19 Cohort. Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis, representing 555 distinct patients, most of which had single timepoints. Regression models adjusted for demographics, risk factors, and comorbidities, were used to determine metabolites associated with predisposition to and/or persistent effects of COVID-19 severity, and metabolite changes that were transient/lingering over the disease course. Sphingolipids/phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were acutely elevated, reflecting the particular importance of pyrimidine metabolism in active COVID-19. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. Our results lay the groundwork for identifying putative biomarkers and preventive strategies for severe COVID-19.

Muscle fiber composition affects the postmortem redox characteristics of yak beef.

Yak infraspinatus (IS), longissimus thoracis (LT), and semitendinosus (ST) muscles were used to explore relationships between myofiber types and postmortem redox characteristics. IS mainly consisted of myofiber type Ⅰ (49.2%), LT has a vast majority of type IIa (72.7%), while ST possessed a similar percentage of type IIa (44.7%) and IIb (51.5%). Compared with LT and ST, IS exhibited higher initial H2O2, myoglobin (T-Mb), and metmyoglobin (MetMb) contents that provoked severe protein oxidation despite higher endogenous antioxidative capacity (e.g., glutathione antioxidative system). Three muscles showed specificities in myofiber type composition and redox characteristics, which were strongly correlated. Specifically, type Ⅰ myofiber positively correlated with H2O2, T-Mb, and multiple antioxidase activity/content while negatively correlated with lipid peroxidation, MetMb, and lactic dehydrogenase activity; also, they tended to employ more SFAs in more intermuscular fat assembly. Overall, muscle-specific myofiber type/redox attributes required differentiated processing to prevent meat oxidation and produce standardized products.

Functional Prediction of trans-Prenyltransferases Reveals the Distribution of GFPPSs in Species beyond the Brassicaceae Clade.

Terpenoids are the most diverse class of plant primary and specialized metabolites, and trans-prenyltransferases (trans-PTs) are the first branch point to synthesize precursors of various chain lengths for further metabolism. Whereas the catalytic mechanism of the enzyme is known, there is no reliable method for precisely predicting the functions of trans-PTs. With the exponentially increasing number of available trans-PTs genes in public databases, an in silico functional prediction method for this gene family is urgently needed. Here, we present PTS-Pre, a web tool developed on the basis of the "three floors" model, which shows an overall 86% prediction accuracy for 141 experimentally determined trans-PTs. The method was further validated by in vitro enzyme assays for randomly selected trans-PTs. In addition, using this method, we identified nine new GFPPSs from different plants which are beyond the previously reported Brassicaceae clade, suggesting these genes may have occurred via convergent evolution and are more likely lineage-specific. The high accuracy of our blind prediction validated by enzymatic assays suggests that PTS-Pre provides a convenient and reliable method for genome-wide functional prediction of trans-PTs enzymes and will surely benefit the elucidation and metabolic engineering of terpenoid biosynthetic pathways.

Understanding Family Tourism: A Perspective of Bibliometric Review.

The study performed bibliometric visual analyses of family tourism research literature from 2008 to 2021, revealing the knowledge evolution process, research focuses, and future trends in this field. A total of 132 articles on family tourism were collated from the SSCI database of the Web of Sciences core collection and analyzed by CiteSpace. The results show that the number of research studies on family tourism has increased from 2008 to 2021, however, the overall base is small. Purdue University has the highest number of publications and citations. Inter-country cooperation occurs between the United States, China, the United Kingdom, and Australia. Recently, "motivation" and "benefit" have become hot topics in family tourism research, and "social tourism" has received widespread attention, revealing future research directions. Lehto and Wu are the core figures in the family tourism field, and their achievements have been highly cited and peer-recognized. This study focuses on family tourism research in different cultural situations, enriching the knowledge system of family tourism research, and encouraging future family tourism research focus more on seniors and disadvantaged families.

Disparities in geographic access to medical oncologists.

OBJECTIVE: The objective of this study is to identify disparities in geographic access to medical oncologists at the time of diagnosis. DATA SOURCES/STUDY SETTING: 2014-2016 Pennsylvania Cancer Registry (PCR), 2019 CMS Base Provider Enrollment File (BPEF), 2018 CMS Physician Compare, 2010 Rural-Urban Commuting Area Codes (RUCA), and 2015 Area Deprivation Index (ADI). STUDY DESIGN: Spatial regressions were used to estimate associations between geographic access to medical oncologists, measured with an enhanced two-step floating catchment area measure, and demographic characteristics. DATA COLLECTION/EXTRACTION METHODS: Medical oncologists were identified in the 2019 CMS BPEF and merged with the 2018 CMS Physician Compare. Provider addresses were converted to longitude-latitude using OpenCage Geocoder. Newly diagnosed cancer patients in each census tract were identified in the 2014-2016 PCR. Census tracts were classified based on rurality and socioeconomic status using the 2010 RUCA Codes and the 2015 ADI. PRINCIPAL FINDINGS: Large towns and rural areas were associated with spatial access ratios (SPARs) that were 6.29 lower (95% CI -16.14 to 3.57) and 14.76 lower (95% CI -25.14 to -4.37) respectively relative to urban areas. Being in the fourth ADI quartile (highest disadvantage) was associated with a 12.41 lower SPAR (95% CI -19.50 to -5.33) relative to the first quartile. The observed difference in a census tract's non-White population from the 25th (1.3%) to the 75th percentile (13.7%) was associated with a 13.64 higher SPAR (Coefficient = 1.10, 95% CI 11.89 to 15.29; p < 0.01), roughly equivalent to the disadvantage associated with living in the fourth ADI quartile, where non-White populations are concentrated. CONCLUSIONS: Rurality and low socioeconomic status were associated with lower geographic access to oncologists. The negative association between area deprivation and geographic access is of similar magnitude to the positive association between larger non-White populations and access. Policies aimed at increasing geographic access to care should be cognizant of both rurality and socioeconomic status.